RT Journal Article
T1 Spatially restricted JAG1-Notch signaling in human thymus provides suitable DC developmental niches
A1 Martín Gayo, Enrique
A1 González García, Sara
A1 García León, María J.
A1 Murcia Ceballos, Alba
A1 Alcain, Juan
A1 García Peydró, Marina
A1 Allende Martínez, Luis Miguel
A1 De Andrés, Belén
A1 Gaspar, María L.
A1 Toribio, María L.
AB A key unsolved question regarding the developmental origin of conventional and plasmacytoid dendritic cells (cdcs and pdcs, respectively) resident in the steady-state thymus is whether early thymic progenitors (EtPs) could escape t cell fate constraints imposed normally by a notch-inductive microenvironment and undergo dc development. By modeling dc generation in bulk and clonal cultures, we show here that Jagged1 (JAG1)-mediated notch signaling allows human EtPs to undertake a myeloid transcriptional program, resulting in GAtA2-dependent generation of cd34+ cd123+ progenitors with restricted pdc, cdc, and monocyte potential, whereas delta-like1 signaling down-regulates GAtA2 and impairs myeloid development. Progressive commitment to the dc lineage also occurs intrathymically, as myeloid-primed cd123+ monocyte/dc and common dc progenitors, equivalent to those previously identified in the bone marrow, are resident in the normal human thymus. the identification of a discrete JAG1+ thymic medullary niche enriched for dc-lineage cells expressing notch receptors further validates the human thymus as a dc-poietic organ, which provides selective microenvironments permissive for dc development.
PB Rockefeller University Press
SN 0022-1007
YR 2017
FD 2017-09-25
LK https://hdl.handle.net/20.500.14352/115701
UL https://hdl.handle.net/20.500.14352/115701
LA eng
NO Martín-Gayo E, González-García S, García-León MJ, Murcia-Ceballos A, Alcain J, García-Peydró M, Allende L, de Andrés B, Gaspar ML, Toribio ML. Spatially restricted JAG1-Notch signaling in human thymus provides suitable DC developmental niches. J Exp Med. 2017 Nov 6;214(11):3361-3379. doi: 10.1084/jem.20161564.
NO European Commission
NO Ministerio de Ciencia e Innovación (España)
NO Instituto de Salud Carlos III (España)
DS Docta Complutense
RD 15 abr 2025